32 Adenovirus Inhibition of Cellular Protein Synthesis and Preferential Translation of Viral mRNAs

Abstract

Human adenovirus dominates host cell protein synthesis, implementing sophisticated approaches that assure the exclusive translation of viral mRNAs while simultaneously suppressing those of the cell. Adenovirus also blocks the host cell antiviral response that would normally inhibit viral translation. Consequently, adenovirus–host cell interactions at the level of translation are complex. The current understanding of translational control in adenovirus-infected cells is discussed here, with a particular emphasis on establishing likely mechanisms for translational dominance of the host cell. A more detailed discussion of specific features of infection by adenovirus, and of host cell–virus interactions, can be found elsewhere (Schneider and Shenk 1987; Mathews and Shenk 1991; Schneider 1996; Chapter 8).

OVERVIEW OF ADENOVIRUS INFECTION AND GENE EXPRESSION
Adenoviruses infect a variety of tissues in humans and animals. The virus contains a double-stranded linear DNA genome, typically 36 kb in size. Adenovirus gene expression is organized into early and late phases, corresponding to expression of genes prior to, or subsequent to, viral DNA replication, respectively. Gene products synthesized during the early phase of infection are associated with functions typically required for viral DNA replication, suppression of host immune recognition, and activation of late viral genes. Late gene products encode structural and nonstructural polypeptides that are required in large amounts for assembly of viral capsids. A detailed understanding of adenovirus biology (and the discussion herein) is restricted largely to human viruses, particularly serotypes 2, 5, 7, 9, and 12.

Early adenovirus gene expression takes place in the nucleus using cellular RNA...